The 6-membered lactone ring of simvastatin is hydrolyzed in vivo to generate the beta, delta-dihydroxy acid, an active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme. Interference with the activity of this enzyme reduces the quantity of mevalonic acid, a precursor of cholesterol.
Simvastatin, the methylated form of lovastatin, is an oral antilipemic agent which inhibits HMG-CoA reductase. simvastatin is used in the treatment of primary hypercholesterolemia and is effective in reducing total and LDL-cholesterol as well as plasma triglycerides and apolipoprotein B.
Hepatic, simvastatin is a substrate for CYP3A4.